POS1329 SECONDARY HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: A SINGLE-CENTRE EXPERIENCE
Authors: R. Thomas, H. Quah, R. Stratton, A. Singh
Journal: Annals of the Rheumatic Diseases (2022)

Background Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterised by fever, organomegaly, cytopaenias, activated macrophages in haematopoietic organs and elevated ferritin. Primary HLH is caused by inherited defects in cytolytic pathway proteins and manifests in infancy [1] . Secondary HLH (sHLH) develops in individuals with a genetic susceptibility to hyperinflammation triggered by strongly immunogenic stimulus such as autoimmune conditions, haematological malignancy, organ transplantation or infection [2] . We present a cohort of patients with sHLH and detail their characteristics. Objectives To evaluate the characteristics and aetiology of sHLH patients at our Centre. Methods A single-centre retrospective observational study of all cases of sHLH between January 2018 and July 2021. Patients were identified from referrals and included if there was a diagnosis of HLH made by a rheumatologist with an H-score of 169 or greater. P-values were calculated using the Mann-Whitney test, unpaired t-test or Fisher exact as appropriate. Results 30 patients (10 female) with sHLH were identified with a median age of 46, a mean H-score of 238 (range 186-317). 15 (50%) had pre-existing immunosuppression, which did not influence mortality (p=0.26). The following primary drivers were identified: lymphoma (n=8), non-HIV viral infections (n=9), first presentation of HIV/AIDS with opportunistic infections (n=4), Adult-onset Still’s disease (n=4), miliary tuberculosis (n=1), M. falciparum infection (n=1), meningococcal meningitis (n=1), checkpoint inhibitor therapy-related (n=1), and no diagnosis (n=1) - Table 1. Table 1. § = Mann Whitney U test, τ = unpaired t-test, φ = Fisher exact Total (n=30) Survived (n=18) Died (n=12) p-value Demographics Male 20 10 10 0.78 § Female 10 8 2 Mean age 43 41 47 0.348 § Median H-score 240 230 254 0.059 τ Ferritin (ng/ml) 40277 34690 48404 0.0949 Trilineage cytopenia, n (%) 9 (33%) 5 (31%) 4 (36%) 0.28 § Subgroup (not mutually exclusive ) 1 yr survival Lymphoma 8 1 7 12.5% (p=0.0025 φ ) HIV/AIDS 4 4 0 100% AOSD 4 4 0 100% Transplant recipient 4 1 3 25% Other viral infection 9 5 4 44% HSV 3 3 0 100% CMV 1 1 0 100% EBV 1 0 1 0% Yellow fever 2 0 2 0% Influenza A 1 1 0 100% Tuberculosis 3 2 1 66% w ith HIV 2 2 0 100% Non-HIV viral infections were the most common cause overall. 6 of 9 were caused by Herpes virus family and all were primary infections. Two followed yellow fever viraemia following live vaccination and both patients died. Mortality varied with aetiology. All four patients with AOSD survived, while 7 of 8 with lymphoma died, as per previous reports 3 . There was a strong association between lymphoma and mortality vs non-lymphoma sHLH (p=0.0025). Four patients post-solid organ transplantation were identified (three liver, one kidney), three with post-transplant lymphoproliferative disorder and one with CMV viraemia (50% mortality). There was no significant difference between age, ferritin or H-score between surviving and deceased patients (Figure 1), but H-score trended higher in the deceased (p=0.059). Number of treatments given for HLH was higher in the deceased group vs survival (mean 3.41 deceased, mean 2.44 in survived). Anakinra was used in all 30 patients as treatment, including as monotherapy in one patient with HSV viraemia who survived. Figure 1. Conclusion Ferritin, H-score at diagnosis or age do not appear to correlate with mortality in sHLH. Lymphoma is associated with a significantly worse outcome. Poor response to treatment and increasing numbers of treatment options is associated with increased mortality. Causes are varied and often co-exist. References [1]Jordan MB et al. An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder. Blood . 2004. [2]Carter SJ et al. Macrophage activation syndrome in adults: recent advances in pathophysiology, diagnosis and treatments. Rheumatology . 2019. [3]Parikh SA et al. Prognostic Factors and Outcomes of Adults with Hemophagocytic Lymphohistiocytosis. Mayo Clin Proc . 2014. Disclosure of Interests None declared